NDLI: APOEε4 alters ApoE and Fabp7 in frontal cortex white matter in prodromal Alzheimer's disease

Content Provider	Springer Nature : BioMed Central
Author	Moreno-Rodriguez, Marta Perez, Sylvia E. Malek-Ahmadi, Michael Mufson, Elliott J.
Abstract	The ApoE ε4 allele (APOEε4) is a major genetic risk factor for sporadic Alzheimer's disease (AD) and is linked to demyelination and cognitive decline. However, its effects on the lipid transporters apolipoprotein E (ApoE) and fatty acid-binding protein 7 (Fabp7), which are crucial for the maintenance of myelin in white matter (WM) during the progression of AD remain underexplored. To evaluate the effects of APOEε4 on ApoE, Fabp7 and myelin in the WM of the frontal cortex (FC), we examined individuals carrying one ε4 allele that came to autopsy with a premortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI) and mild to moderate AD compared with non-carrier counterparts. ApoE, Fabp7 and Olig2 immunostaining was used to visualize cells, whereas myelin basic protein (MBP) immunocytochemistry and luxol fast blue (LFB) histochemistry of myelin in the WM of the FC were combined with quantitative morphometry. We observed increased numbers of ApoE-positive astrocytes in the WM of both NCI and MCI APOEε4 carriers compared with non-carriers, whereas Fabp7-positive cells were elevated only in AD. Conversely, Olig2 cell counts and MBP immunostaining decreased in MCI APOEε4 carriers compared to non-carriers, while LFB levels were higher in NCI APOEε4 carriers compared to non-carriers. Although no correlations were found between ApoE, Fabp7, and cognitive status, LFB measurements were positively correlated with perceptual speed, global cognition, and visuospatial scores in APOEε4 carriers across clinical groups. The present findings suggest that the ε4 allele compromises FC myelin homeostasis by disrupting the lipid transporters ApoE, Fabp7 and myelination early in the onset of AD. These data support targeting cellular components related to WM integrity as possible treatments for AD.
Related Links	https://jneuroinflammation.biomedcentral.com/counter/pdf/10.1186/s12974-025-03349-y.pdf
Ending Page	17
Page Count	17
Starting Page	1
File Format	HTM / HTML
ISSN	17422094
DOI	10.1186/s12974-025-03349-y
Journal	Journal of Neuroinflammation
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2025-01-30
Access Restriction	Open
Subject Keyword	Neurosciences Neurology Neurobiology Immunology APOEε4 Fabp7 Astrocytes White matter Alzheimer's disease Mild cognitive impairment
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology Cellular and Molecular Neuroscience Neurology
Journal Impact Factor	9.3/2023
5-Year Journal Impact Factor	9.8/2023

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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